tbuckley/cabot-search huggingface dataset:
AB1516 A CASE OF SEVERE ANCA ASSOCIATED VASCULITIS AFTER COVID-19 VACCINATION
Authors: I. Qaisar, K. Sunmboye
Journal: Annals of the Rheumatic Diseases (2022)

Background The world is currently rocking to and fro in the midst of the COVID-19 viral storm and vaccinations have played a pivotal role in calming this.Although COVID-19 vaccines have been thoroughly assessed and studied before being rolled out to the general population, there have been reports of post vaccination complications in limited number of subjects strongly associated with COVID-19 vaccinations[1]. Objectives To report a case of severe ANCA associated vasculitis after COVID-19 vaccination. Methods A case report and discussion. Results In view of this, we report the case of a 77 year old caucasian male who developed severe ANCA associated vasculitis (AAV) after two doses of AstraZeneca vaccine and one booster dose of Pfizer COVID-19 booster. He presented with acute onset inflammatory arthritis with mononeuritis multiplex with bilateral foot drop and left radial and ulnar nerve forearm weakness in typical asymmetrical pattern two weeks after the Pfizer vaccination. He had a raised MPO-ANCA titre of 66 IU/ml, C-reactive protein of 131mg/L and reactive thrombocytosis of 458 X 10 9 /L. Nerve conduction study confirmed mononeuritis multiplex in the bilateral peroneal nerves and left radial and ulnar nerve. A total body CT had excluded malignancy and paraneoplastic associations and Gullian-Barre diagnosis was also excluded. The patient was treated with 3 days of intravenous methylprednisolone 1g daily then given intravenous Rituximab 1g, two weeks apart. He is currently undergoing rehabilitation in view of the vasculitic neuropathy from his diagnosis. Conclusion Diagnosis of AAV is often delayed or missed by other medical specialties due to its varied presentation. AAV should be suspected in a patient with paraesthesia/weakness in keeping with mononeuritis multiplex or other peripheral neuropathy in the absence of an alternative explanation (e.g. diabetes,B12 deficiency) and in particular with a wrist or foot drop.Exposure to certain drugs and substances of abuse such as cocaine, hydralazine and propylthiouracil has been implicated with AAV.While short-term side effects of COVID-19 vaccine resemble those of other vaccines, long-term side effects remain unknown[2]. Rare side effects continue to surface as millions of people receive COVID-19 vaccines around the world. References [1] https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19/treatments-vaccines/vaccines-covid-19/safety-covid-19-vaccines [2] https://doi.org/10.1136/bmj.m1070 Disclosure of Interests None declared
Development and validation of a trans-ancestry polygenic risk score for type 2 diabetes in diverse populations
Authors: Tian Ge, Marguerite R. Irvin, Amit Patki, Vinodh Srinivasasainagendra, Yen-Feng Lin, Hemant K. Tiwari, Nicole D. Armstrong, Barbara Benoit, Chia-Yen Chen, Karmel W. Choi, James J. Cimino, Brittney H. Davis, Ozan Dikilitas, Bethany Etheridge, Yen-Chen Anne Feng, Vivian Gainer, Hailiang Huang, Gail P. Jarvik, Christopher Kachulis, Eimear E. Kenny, Atlas Khan, Krzysztof Kiryluk, Leah Kottyan, Iftikhar J. Kullo, Christoph Lange, Niall Lennon, Aaron Leong, Edyta Malolepsza, Ayme D. Miles, Shawn Murphy, Bahram Namjou, Renuka Narayan, Mark J. O’Connor, Jennifer A. Pacheco, Emma Perez, Laura J. Rasmussen-Torvik, Elisabeth A. Rosenthal, Daniel Schaid, Maria Stamou, Miriam S. Udler, Wei-Qi Wei, Scott T. Weiss, Maggie C. Y. Ng, Jordan W. Smoller, Matthew S. Lebo, James B. Meigs, Nita A. Limdi, Elizabeth W. Karlson
Journal: Genome Medicine (2022)

Abstract Background Type 2 diabetes (T2D) is a worldwide scourge caused by both genetic and environmental risk factors that disproportionately afflicts communities of color. Leveraging existing large-scale genome-wide association studies (GWAS), polygenic risk scores (PRS) have shown promise to complement established clinical risk factors and intervention paradigms, and improve early diagnosis and prevention of T2D. However, to date, T2D PRS have been most widely developed and validated in individuals of European descent. Comprehensive assessment of T2D PRS in non-European populations is critical for equitable deployment of PRS to clinical practice that benefits global populations. Methods We integrated T2D GWAS in European, African, and East Asian populations to construct a trans-ancestry T2D PRS using a newly developed Bayesian polygenic modeling method, and assessed the prediction accuracy of the PRS in the multi-ethnic Electronic Medical Records and Genomics (eMERGE) study (11,945 cases; 57,694 controls), four Black cohorts (5137 cases; 9657 controls), and the Taiwan Biobank (4570 cases; 84,996 controls). We additionally evaluated a post hoc ancestry adjustment method that can express the polygenic risk on the same scale across ancestrally diverse individuals and facilitate the clinical implementation of the PRS in prospective cohorts. Results The trans-ancestry PRS was significantly associated with T2D status across the ancestral groups examined. The top 2% of the PRS distribution can identify individuals with an approximately 2.5–4.5-fold of increase in T2D risk, which corresponds to the increased risk of T2D for first-degree relatives. The post hoc ancestry adjustment method eliminated major distributional differences in the PRS across ancestries without compromising its predictive performance. Conclusions By integrating T2D GWAS from multiple populations, we developed and validated a trans-ancestry PRS, and demonstrated its potential as a meaningful index of risk among diverse patients in clinical settings. Our efforts represent the first step towards the implementation of the T2D PRS into routine healthcare.
POS0749 ANTI-Β2GPI-DOMAIN 1 ANTIBODIES STRATIFY HIGH RISK OF EXTRA-CRITERIA MANIFESTATIONS IN A LARGE PROSPECTIVE CHINESE COHORT OF ANTIPHOSPHOLIPID SYNDROME
Authors: Y. Zhou, W. Qi, J. Zhao, M. Li, X. Zeng
Journal: Annals of the Rheumatic Diseases (2022)

Background Anti-β2GPI-Domain 1 (β2GPI-D1) antibodies are potentially pathogenic in patients with antiphospholipid syndrome (APS), but their clinical associations and diagnostic value were unclear. Objectives To evaluate the clinical characteristics of APS patients with anti-β2GPI-D1 positivity, and its utility in diagnosing APS among SLE patients. Methods A total of 338 patients were included, of which 169 patients diagnosed with primary APS (PAPS group), 50 with APS secondary to SLE (SAPS group), 209 with SLE (SLE group). Serum anti-β2GPI-D1 IgG was measured using chemiluminescent immunoassay (Inova Company). Extra-criteria manifestations were analyzed, including thrombocytopenia, autoimmune hemolytic anemia, valvular lesions, APS nephropathy, and non-vascular neurological manifestations. Results Similar presence of anti-β2GPI-D1 IgG was seen among PAPS (32.80%) and SAPS (32.0%) patients, and 96.4% of those with positive anti-β2GPI-D1 IgG showed triple aPLs positivity. Anti-β2GPI-D1 IgG was significantly associated with recurrent thrombosis before APS diagnosis, microscopic thrombosis (p&lt;0.05), but not with adverse pregnancy events (Figure 1). Notably, patients with extra-criteria manifestations, especially thrombocytopenia and APS nephropathy, showed significantly higher titers in anti-β2GPI-D1 IgG (p&lt;0.05). After a median follow-up of twenty-five months, patients with anti-β2GPI-D1 IgG also showed a tendency of more extra-criteria events (3/55 vs 1/114, p=0.095), but not thrombotic events or adverse pregnancy events. Anti-β2GPI-D1 was positive among 8.13% of the SLE controls, and showed higher specificity (91.9%) in diagnosing SAPS among SLE patients as compared to classic aPLs. Figure 1. Conclusion Anti-β2GPI-D1 IgG had a stronger association with extra-criteria manifestations in APS patients compared to three classic APLs, which properly indicated its pathogenic role of microangiopathy. Disclosure of Interests None declared
POS1140 SHORT-TERM EXPOSURE TO FINE PARTICULATE MATTER AND RISK OF FRAGILITY HIP FRACTURES, A CASE-CROSSOVER STUDY ON 1,042 HIP FRACTURES
Authors: G. Adami, M. Pontalti, A. Fassio, C. Benini, D. Gatti, S. Negri, P. Olivi, M. Rossini
Journal: Annals of the Rheumatic Diseases (2022)

Background Fragility femoral fracture is a common, world-spread, medical condition, that has a relevant impact both clinically and economically. Chronic exposure to environmental air pollution has been linked with a higher risk of developing osteoporosis. However, little is known regarding the relationship between short-term exposure to air pollution and bone fractures. Objectives Our study aims to investigate the link between short-term exposure to fine particulate matters and fragility hip fractures Methods We retrieved data of patients suffering of hip fractures admitted to the Orthopedic Unit of the University of Verona Hospital from 2015 to 2020. We retrieved data on the monitoring of PM10 concentrations from the Italian institute of environment protection and research (ISPRA). We designed a case-crossover study to compare the exposure to particulate matters (PM10) in the 30-day period immediately before the fracture (hazard period) referent to a 30-day control period (from day -30 to -60 from the fracture). Exposure to PM10 was evaluated as mean value and AUC. Case-crossover is a peculiar study design applied to longitudinal datasets that controls for within-person time-invariant and between-patient confounders such as indoor air pollution, chronic comorbidities or concomitant medications and have been used extensively to study the effects of transient, short-term exposures on the risk of acute events (Figure 1 A ) Results 1042 patients (73.7% female n=768), with a hip fracture admitted to the hospital were included in the study. Mean age of the cohort was 82.6 years (±9.55). Average exposure to PM 10 in the control period was 33,84 ug/mm3, cumulative exposure (AUC) was 952,42 ug/mm3 compared 31,72 ug/mm3 and AUC of 920,24 ug/mm3 in the hazard period (Figure 1 B ) The difference between levels of PM10 in the two periods was statistically significant as levels of PM10 was higher in the hazard period compared to control period, with a p-value = 0,027 (α &lt;0,05) when comparing average concentrations in the two groups and a p-value = 0,024 (α &lt;0,05), when comparing AUCs. Conclusion Our study suggests that the short-term exposure to environmental air pollution might increase the risk of femoral fragility fractures. Further studies should be taken to further investigate the biological mechanisms underlining this finding. Disclosure of Interests Giovanni Adami Shareholder of: Theramex, Galapagos, Marco Pontalti: None declared, Angelo Fassio: None declared, Camilla Benini: None declared, Davide Gatti: None declared, Stefano Negri: None declared, Pietro Olivi: None declared, Maurizio Rossini Shareholder of: Abbvie, Amgen, Bms, Eli Lilly, Galapagos, Novartis, Pfizer, Sandoz, Theramex, Ucb.
In difficult biliary cannulation, how quickly should we be reaching for the second wire?
Authors: Harry Martin, George Webster
Journal: Endoscopy (2022)

See also: Early double-guidewire versus repeated single-guidewire technique to facilitate selective bile duct cannulation: a randomized controlled trialEndoscopy 2022; 54(02): 120-127DOI: 10.1055/a-1395-7485
Immunodominant MHC-II (Major Histocompatibility Complex II) Restricted Epitopes in Human Apolipoprotein B
Authors: Payel Roy, John Sidney, Cecilia S. Lindestam Arlehamn, Elizabeth Phillips, Simon Mallal, Sujit Silas Armstrong Suthahar, Monica Billitti, Paul Rubiro, Daniel Marrama, Fabrizio Drago, Jenifer Vallejo, Vasantika Suryawanshi, Marco Orecchioni, Jeffrey Makings, Paul J. Kim, Coleen A. McNamara, Bjoern Peters, Alessandro Sette, Klaus Ley
Journal: Circulation Research (2022)

Background: CD (cluster of differentiation) 4 + T-cell responses to APOB (apolipoprotein B) are well characterized in atherosclerotic mice and detectable in humans. CD4 + T cells recognize antigenic peptides displayed on highly polymorphic HLA (human leukocyte antigen)-II. Immunogenicity of individual APOB peptides is largely unknown in humans. Only 1 HLA-II-restricted epitope was validated using the DRB1*07:01-APOB 3036 –3050 tetramer. We hypothesized that human APOB may contain discrete immunodominant CD4 + T-cell epitopes that trigger atherosclerosis-related autoimmune responses in donors with diverse HLA alleles. Methods: We selected 20 APOB-derived peptides (APOB 20 ) from an in silico screen and experimentally validated binding to the most commonly occurring human HLA-II alleles. We optimized a restimulation-based workflow to evaluate antigenicity of multiple candidate peptides in HLA-typed donors. This included activation-induced marker assay, intracellular cytokine staining, IFNγ (interferon gamma) enzyme–linked immunospot and cytometric bead array. High-throughput sequencing revealed TCR (T-cell receptor) clonalities of APOB-reactive CD4 + T cells. Results: Using stringent positive, negative, and crossover stimulation controls, we confirmed specificity of expansion-based protocols to detect CD4 + T cytokine responses to the APOB 20 pool. Ex vivo assessment of AIM + CD4 + T cells revealed a statistically significant autoimmune response to APOB 20 but not to a ubiquitously expressed negative control protein, actin. Resolution of CD4 + T responses to the level of individual peptides using IFNγ enzyme–linked immunospot led to the discovery of 6 immunodominant epitopes (APOB 6 ) that triggered robust CD4 + T activation in most donors. APOB 6 -specific responding CD4 + T cells were enriched in unique expanded TCR clonotypes and preferentially expressed memory markers. Cytometric bead array analysis detected APOB 6 -induced secretion of both proinflammatory and regulatory cytokines. In clinical samples from patients with angiographically verified coronary artery disease, APOB 6 stimulation induced higher activation and memory phenotypes and augmented secretion of proinflammatory cytokines TNF (tumor necrosis factor) and IFNγ, compared with patients with low coronary artery disease. Conclusions: Using 3 cohorts, each with ≈20 donors, we discovered and validated 6 immunodominant, HLA-II–restricted APOB epitopes. The immune response to these APOB epitopes correlated with coronary artery disease severity.
AB0993 INDICATORS OF BONE MINERAL DENSITY IN ELDERLY AND SENILE MALE PATIENTS WITH OSTEOARTHRITIS OF THE KNEE JOINT, DEPENDING ON THE STATE OF THE MUSCULAR APPARATUS
Authors: O. Malyshenko, M. Letaeva, T. Raskina, J. Averkieva, M. Koroleva
Journal: Annals of the Rheumatic Diseases (2022)

Objectives To evaluate bone mineral density (BMD) indicators in elderly and senile male patients with osteoarthritis (OA) of the knee joint, depending on the state of the muscular apparatus. Methods The study included 32 patients with an established diagnosis of knee joint OA. The average age of patients was 68.7 (66.1; 70.3) years. The diagnosis of knee joint OA was established according to the diagnostic criteria of the American College of Rheumatology (ACR, 1991). For comparative analysis, all patients were divided into 3 groups depending on the state of the muscular apparatus (EWGSOP, 2010: muscle mass was assessed by multispiral computed tomography, muscle strength was measured using a wrist dynamometer, muscle function was examined using a battery of short tests): 1st – 9 patients without sarcopenia, 2nd - 11 patients with presarcopenia and 3rd - 12 patients with sarcopenia. BMD was assessed by two-energy X-ray absorptiometry in the neck and proximal femur as a whole and in the lumbar spine. Results Osteopenic syndrome in the study cohort was diagnosed in 23 (71.9%) patients: osteopenia - in 19 (59.4%) patients, osteoporosis – in 4 (12.5%). Normal BMD values were observed in 9 (28.1%) patients. Osteopenic syndrome was detected in patients with sarcopenia significantly more often than in patients without sarcopenia (p&gt;0.05) and with presarcopenia (p=0.05). Thus, in the group of patients without sarcopenia, normal BMD indicators were noted in 6 (18.8%) patients, OPe – in 3 (9.4%), no cases of OP were detected. In patients with presarcopenia, normal BMD indicators were determined in 3 (9.4%) patients, OPe - in 8 (25%) patients, no cases of OP were also detected. In patients with sarcopenia, normal BMD indicators were not registered, OPS was detected in 12 (37.5%) patients, while OPe – in 8 (25.0%) and OP – in 4 (12.5%). BMD in patients with sarcopenia in the neck and proximal femur as a whole were statistically significantly lower than in patients without sarcopenia and with presarcopenia (p&lt;0.050). The BMD in the femoral neck in patients with sarcopenia was 0.908 [0.817; 0.977] g/cm2, which corresponds to -0.95 [-1.35; 0.425] CO according to the T-criterion, while in the groups of patients without sarcopenia and with presarcopenia, statistically significantly higher BMD values were recorded: 0.998 [0.935; 1.09] g/cm2 and 0.995 [0.94; 1.04] g/cm2 (p=0.009 and p=0.027), which corresponds to -0.30 [-0.80; 0.225] and -0.30 [-0.70; 0] CO according to the T-criterion (p= 0.013 and p=0.024), respectively. When comparing the BMD and T-test in the lumbar spine, there were no statistically significant differences in the studied groups of patients. Conclusion Sarcopenia is associated with low BMD in the neck and proximal femur in general in elderly and senile male patients with knee joint OA. Disclosure of Interests None declared
AB0228 THE CONNECTION BETWEEN NUTRITIONAL STATUS AND DISEASE ACTIVITY IN RHEUMATOID ARTHRITIS
Authors: L. Huang, Y. Huang, M. Liu, Q. Huang, Z. Ji, S. Sun, W. Deng, T. W. Li
Journal: Annals of the Rheumatic Diseases (2022)

Background Nutritional status is closely associated with a person’s physical condition. As for patients with autoimmune disease, nutritional status may affect the balance of immune system, which successively affects disease activity. Objectives The prognostic nutritional index (PNI), nutritional risk index (NRI), controlling nutritional status (CONUT) score and body mass index (BMI) are four widely used nutritional indices [1]. This study aimed to investigate the relationship between nutritional status and disease activity of rheumatoid arthritis (RA). Methods 168 RA patients and 50 healthy volunteers were retrospectively enrolled. According to the disease activity score using 28 joint counts-erythrocyte sedimentation rate (DAS28-ESR), the cohort of RA patients was divided into the lower disease activity groups (DAS28-ESR≤3.2) and the higher disease activity groups (DAS28-ESR&gt;3.2). We recorded clinical assessment and laboratory data for further analysis. Spearman’s correlation, receiver operation characteristic (ROC) curves, binary logistic regression analysis were carried out. Results Compared to the higher disease activity group, the lower disease activity group had low-level total protein (TP), ESR and CRP (all P&lt;0.05), while high-level albumin and PNI (all P&lt;0.05). PNI and NRI were negatively correlated with DAS28-ESR (r=-0.395, and r=-0.200, all P&lt;0.05), while CONUT score was positively correlated with DAS28-ESR (r=0.324, P&lt;0.05). ROC curve illustrated that area under the curve (AUC) of PNI for RA patients with higher disease activity was superior to NRI, CONUT score and BMI. The AUC of PNI was 0.693. Figure 1. The diagnostic value of variables for disease activity in rheumatoid arthritis using ROC curve Table 1. The correlation between nutritional indices and disease activity score using 28 joint counts-erythrocyte sedimentation rate (DAS28-ESR ) PNI NRI CONUT score BMI r P value r P value r P value r P value Neutrophil(×10 9 /L) -0.061 0.434 0.045 0.568 0.025 0.757 0.079 0.313 Monocyte(×10 9 /L) 0.183 0.163 0.145 0.064 -0.104 0.193 0.152 0.052 Lymphocyte(×10 9 /L) 0.472 0.000 0.201 0.010 -0.436 0.000 0.208 0.007 ESR (mm/h) -0.561 0.000 -0.258 0.001 0.393 0.000 -0.182 0.020 CRP (mg/L) -0.520 0.000 -0.077 0.326 0.391 0.000 0.003 0.967 RF(IU/ml) -0.224 0.004 -0.116 0.151 0.260 0.001 -0.082 0.306 CCP(IU/ml) -0.139 0.088 -0.201 0.014 0.195 0.018 -0.188 0.022 DAS28-ESR -0.395 0.000 -0.200 0.011 0.324 0.000 -0.142 0.072 Conclusion PNI may become a manageable marker for detector disease activity of RA patients. References [1]Ahn, S.S., et al., Comparison of the Clinical Implications among Five Different Nutritional Indices in Patients with Lupus Nephritis. Nutrients, 2019. 11(7). Disclosure of Interests None declared
AB1467 EPIDEMIOLOGICAL DESCRIPTION OF JUVENILE IDIOPATHIC ARTHRITIS FROM A COLOMBIAN POPULATION
Authors: M. D. Canola Escobar, D. Rodriguez-Ariza, L. Aaron-Infante, D. Cardona, Y. Hernandez-Arenas, D. Melo, J. Puentes, P. Rozo-Tellez, V. Usuga-Graciano, O. Ariza-Quintero
Journal: Annals of the Rheumatic Diseases (2022)

Background Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood and presents predominantly with peripheral arthritis; this pathology is divided into subgroups. In Colombia there are few descriptive studies. Objectives The objective was to describe the sociodemographic, immunological and clinical characteristics of a cohort of patients with Juvenile Idiopathic Arthritis. Methods An observational cross-sectional study was conducted that included 171 JIA patients treated at a specialized rheumatology institution between 2010 and 2021. Univariate analyzes were performed to describe the sociodemographic, immunological, and clinical profile of the population. The epidemiological characteristics were obtained from the review of medical reports. Results 171 patients were analyzed. 58.48% were women; with a median age at diagnosis of 12.25 years (IQR=6.55), and a median duration of the disease of 3.71 years (IQR=5.52). According to the classification criteria of the International League of Associations for Rheumatism (ILAR), the most frequent were enthesitis related to JIA present in 61 patients (35.67%), oligoarticular 27 (15.79%), negative polyarticular rheumatoid factor (14.62%) and positive polyarticular rheumatoid factor (14.04%). JIA-enthesitis related was 17,85% ANAs positive, 16,66% rheumatoid factor positive and HLA-B27 en 22,72%. In JIA oligoarticular the auto-antibodies ANAS, FR was present in 26,32% and 16,66%. The JIA-polyarticular rheumatoid factor positive was positive for ANA in 76.47% and AntiCCP in 88.88%. JIA-polyarticular rheumatoid factor negative was positive for ANAs (40%) and AntiCCP (10%). Conclusion The epidemiological description of JIA in the Colombian population is similar to the current one in other populations, but we found differences in the subtypes of juvenile idiopathic arthritis and in the presence of autoantibodies. This is the first step to discover the characteristics of this autoimmune disease in this population. Disclosure of Interests Miguel Dario Canola Escobar: None declared, DANIEL RODRIGUEZ-ARIZA: None declared, LUIS AARON-INFANTE: None declared, DIANA CARDONA: None declared, YADITH HERNANDEZ-ARENAS: None declared, DIEGO MELO: None declared, JUAN PUENTES: None declared, PAULA ROZO-TELLEZ: None declared, Veronica Usuga-Graciano: None declared, OLGA ARIZA-QUINTERO Employee of: actual employee in Novartis Colombia as medical science liaison